The invention relates to systems and methods for treating neurological disorders, and more particularly to a system and method employing an electronic device for sensing and detecting neurological dysfunction, specifically neuronal activity characteristic of epileptic seizures, in one region of a patient""s brain, and applying treatment in response thereto in another region of the patient""s brain.
Epilepsy, a neurological disorder characterized by the occurrence of seizures (specifically episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or the perturbation of the autonomic nervous system), is debilitating to a great number of people. It is believed that as many as two to four million Americans may suffer from various forms of epilepsy. Research has found that its prevalence may be even greater worldwide, particularly in less economically developed nations, suggesting that the worldwide figure for epilepsy sufferers may be in excess of one hundred million.
Because epilepsy is characterized by seizures, its sufferers are frequently limited in the kinds of activities they may participate in. Epilepsy can prevent people from driving, working, or otherwise participating in much of what society has to offer. Some epilepsy sufferers have serious seizures so frequently that they are effectively incapacitated.
Furthermore, epilepsy is often progressive and can be associated with degenerative disorders and conditions. Over time, epileptic seizures often become more frequent and more serious, and in particularly severe cases, are likely to lead to deterioration of other brain functions (including cognitive function) as well as physical impairments.
The current state of the art in treating neurological disorders, particularly epilepsy, typically involves drug therapy and surgery. The first approach is usually drug therapy.
A number of drugs are approved and available for treating epilepsy, such as sodium valproate, phenobarbital/primidone, ethosuximide, gabapentin, phenytoin, and carbamazepine, as well as a number of others. Unfortunately, those drugs typically have serious side effects, especially toxicity, and it is extremely important in most cases to maintain a precise therapeutic serum level to avoid breakthrough seizures (if the dosage is too low) or toxic effects (if the dosage is too high). The need for patient discipline is high, especially when a patient""s drug regimen causes unpleasant side effects the patient may wish to avoid.
Moreover, while many patients respond well to drug therapy alone, a significant number (at least 20-30%) do not. For those patients, surgery is presently the best-established and most viable alternative course of treatment.
Currently practiced surgical approaches include radical surgical resection such as hemispherectomy, corticectomy, lobectomy and partial lobectomy, and less-radical lesionectomy, transection, and stereotactic ablation. Besides being less than fully successful, these surgical approaches generally have a high risk of complications, and can often result in damage to eloquent (i.e., functionally important) brain regions and the consequent long-term impairment of various cognitive and other neurological functions. Furthermore, for a variety of reasons, such surgical treatments are contraindicated in a substantial number of patients. And unfortunately, even after radical brain surgery, many epilepsy patients are still not seizure-free.
Electrical stimulation is an emerging therapy for treating epilepsy. However, currently approved and available electrical stimulation devices apply continuous electrical stimulation to neural tissue surrounding or near implanted electrodes, and do not perform any detectionxe2x80x94they are not responsive to relevant neurological conditions.
The NeuroCybernetic Prosthesis (NCP) from Cyberonics, for example, applies continuous electrical stimulation to the patient""s vagus nerve. This approach has been found to reduce seizures by about 50% in about 50% of patients. Unfortunately, a much greater reduction in the incidence of seizures is needed to provide clinical benefit. The Activa device from Medtronic is a pectorally implanted continuous deep brain stimulator intended primarily to treat Parkinson""s disease. In operation, it supplies a continuous electrical pulse stream to a selected deep brain structure where an electrode has been implanted.
A typical epilepsy patient experiences episodic attacks or seizures, which are generally defined as periods of abnormal neurological activity. As is traditional in the art, such periods shall be referred to herein as xe2x80x9cictalxe2x80x9d (though it should be noted that xe2x80x9cictalxe2x80x9d can refer to neurological phenomena other than epileptic seizures).
Known work on detection and treatment of epilepsy via electrical stimulation has focused on a region of the brain frequently referred to as an epileptic (or epileptogenic) focus, particularly in patients suffering from partial epilepsy (the most common form of adult-onset epilepsy). In at least some partial epilepsy sufferers, it is the area where hypersynchronous activity consistently begins; it typically spreads outward, and into other regions of the brain, from there. The characteristics of an epileptic seizure onset are different from patient to patient, but are frequently consistent from seizure to seizure within a single patient. Although seizures in a partial epilepsy sufferer frequently begin in the same region of the brain, they may secondarily generalize quickly to cover a significant portion of the brain. Patients with primary generalized epilepsy may not have any specific identifiable seizure origin.
Unfortunately, continuous stimulation of deep brain structures for the treatment of epilepsy has not met with consistent success. To be effective in terminating seizures, it has traditionally been believed that epilepsy stimulation should be performed near the focus of the epileptogenic region. The focus is often in the neocortex, where continuous stimulation may cause significant neurological deficit with clinical symptoms including loss of speech, sensory disorders, or involuntary motion. Accordingly, research has been directed toward automatic responsive epilepsy treatment at or near the focus, based on a detection of imminent seizure.
Recent research, however, indicates that the concept of a single epileptic focus does not necessarily accurately reflect the origins of partial epilepsy, at least in humans. See J. Engel, Jr., Intracerebral Recordings: Organization of the Human Epileptic Region, J. Clin. Neurophysiol. 1993; 10(1): 90-98. The human brain is a complex system, and although an anomalous signal may first be detected via known methods at a particular location or region, that does not necessarily imply that area is the true epileptogenic origin of an epileptic seizure. Nor is the region where abnormal signals are first identified necessarily the location where it is most effective to treat a seizure or its precursor. In fact, it is possible to have multiple locations in a single patient""s brain that all act as epileptic foci. And in generalized seizures, abnormal EEG signals can be found throughout a patient""s brain practically simultaneously.
Most prior work on the detection and responsive treatment of seizures via electrical stimulation has focused on analysis of electroencephalogram (EEG) and electrocorticogram (ECoG) waveforms. In general, EEG signals represent aggregate neuronal activity potentials detectable via electrodes applied to a patient""s scalp, and ECoGs use internal electrodes near the surface of the brain. ECoG signals, deep-brain counterparts to EEG signals, are also detectable via electrodes implanted under the dura mater, and usually within the patient""s brain. Unless the context clearly and expressly indicates otherwise, the term xe2x80x9cEEGxe2x80x9d shall be used generically herein to refer to both EEG and ECoG signals.
Much of the work on detection has focused on the use of time-domain analysis of EEG signals. See, e.g., J. Gotman, Automatic seizure detection: improvements and evaluation, Electroencephalogr. Clin. Neurophysiol. 1990; 76(4): 317-24. In a typical time-domain detection system, EEG signals are received by one or more implanted electrodes and then processed by a control module, which then is capable of performing an action (intervention, warning, recording, etc.) when an abnormal event is detected.
In the Gotman system, EEG waveforms are filtered and decomposed into xe2x80x9cfeaturesxe2x80x9d representing characteristics of interest in the waveforms. One such feature is characterized by the regular occurrence (i.e., density) of half-waves exceeding a threshold amplitude occurring in a specified frequency band between approximately 3 Hz and 20 Hz, especially in comparison to background (non-ictal) activity. When such half-waves are detected, the onset of a seizure is identified. For related approaches, see also H. Qu and J. Gotman, A seizure warning system for long term epilepsy monitoring, Neurology 1995; 45: 2250-4; and H. Qu and J. Gotman, A Patient-Specific Algorithm for the Detection of Seizure Onset in Long-Term EEG Monitoring: Possible Use as a Warning Device, IEEE Trans. Biomed. Eng. 1997; 44(2): 115-22.
A more computationally demanding approach is to transform EEG signals into the frequency domain for rigorous spectrum analysis. See, e.g., U.S. Pat. No. 5,995,868 to Dorfmeister et al., which analyzes the power spectral density of EEG signals in comparison to background characteristics. Although this approach is generally believed to achieve good results, for the most part, its computational expense renders it less than optimal for use in long-term implanted epilepsy monitor and treatment devices. With current technology, the battery life in an implantable device computationally capable of performing the Dorfmeister method would be too short for it to be feasible.
Also representing an alternative and more complex approach is U.S. Pat. No. 5,857,978 to Hively et al., in which various non-linear and statistical characteristics of EEG signals are analyzed to identify the onset of ictal activity. Once more, the calculation of statistically relevant characteristics is not believed to be feasible in an implantable device.
U.S. Pat. No. 6,016,449 to Fischell, et al., entitled xe2x80x9cSystem for Treatment of Neurological Disorders,xe2x80x9d which is hereby incorporated by reference as though set forth in full herein, describes an implantable seizure detection and treatment system. In the Fischell system, various detection methods are possible, all of which essentially rely upon the analysis (either in the time domain or the frequency domain) of processed EEG signals. Fischell""s controller is preferably implanted intracranially, but other approaches are also possible, including the use of an external controller. When a seizure is detected, the Fischell system applies responsive electrical stimulation to terminate the seizure, a capability that will be discussed in further detail below.
All of these approaches provide useful information, and in some cases may provide sufficient information for accurate detection and prediction of most imminent epileptic seizures.
Accordingly, as has been previously suggested, it is possible to treat and terminate seizures by applying electrical stimulation to the brain. See, e.g., U.S. Pat. No. 6,016,449 to Fischell et al., and H. R. Wagner, et al., Suppression of cortical epileptiform activity by generalized and localized ECoG desynchronization, Electroencephalogr. Clin. Neurophysiol. 1975; 39(5): 499-506. It should be noted, however, that the epilepsy detection methods described above rely, at least in part, on the continuous analysis of EEG signals. To the extent responsive electrical stimulation is applied in response to a detection of epileptiform activity, artifacts of the stimulation received by the epileptiform activity detector may be significantly disruptive of the detection algorithms. A potential solution to this problem is to blank the sensing amplifiers used to receive EEG signals during and for a period after the application of electrical stimulation, but this will lead to a loss of data during the blanking period.
To recapitulate somewhat, in general, partial epilepsy is a much more complex phenomenon than traditionally thought. It is believed to be advantageous to provide therapeutic electrical stimulation in a number of brain regions involved in a patient""s epilepsy, but known approaches do not do this in any meaningful way. Given the neural organization of the brain, in a given patient it may be more effective to stimulate pathways associated with epileptogenic focus, rather than the focus itself, to disrupt or block the epileptiform activity to prevent the occurrence of a clinical seizure. It is anticipated that stimulation from contralateral structures, particularly when the focus is hippocampal, may be the preferred method of treating some types of spontaneously occurring epileptiform activity. In addition, it may be particularly advantageous to apply electrical stimulation exclusively in areas distant from an epileptogenic region, as electrical stimulation of neural tissue that is especially sensitive may contribute to or initiate the hypersynchronous activity that characterizes an epileptic seizure. And furthermore, remote stimulation would serve to advantageously reduce the effects of artifacts on, the epilepsy detection methods employed.
Accordingly, a system and method according to the invention for treating a neurological disorder such as epilepsy includes an implantable electronic device capable of detecting seizure activity and its precursors, as well as providing responsive electrical stimulation to brain tissue.
The treatment methods of the present invention can be accomplished with a number of different approaches. In a typical embodiment, an implantable neurostimulator will have at least two electrodes near or in contact with brain tissue. Those electrodes may be located in close proximity to each other on a single lead, or may be on separate leads in entirely different portions of the brain. Each electrode may be dedicated to a single purpose, either detection or stimulation, or may be switchable between detection and stimulation functions.
Sensing and stimulating electrodes according to the invention are situated in different regions of the patient""s brain. The regions may be physically or functionally distinct, but at least one set of sensing and stimulating electrodes should be remote from each other to facilitate the advantages and avoid the disadvantages set forth above.
Several potential regions of interest for remote sensing and stimulation have been identified. As used herein, xe2x80x9cremote sensing and stimulationxe2x80x9d means sensing in one area of the brain and stimulating in another area. In particular, several of these regions are described in greater detail in the Engel article referenced above, and will be further characterized in the detailed description below.
Remote sensing and stimulation according to the invention is not necessarily constrained to being an exclusive therapy; it may be advantageously performed in concert with other treatment modalities, such as responsive drug infusion, somatosensory stimulation (including audio stimulation), or vagus nerve stimulation. Remote sensing and stimulation may also, in certain circumstances, be advantageously combined with electrical stimulation at or, near the epileptogenic region, or where a seizure or its onset is first detected.
In any event, by way of the present invention, neurological signals are received by at least one electrode and analyzed by the implantable neurostimulator to identify an epileptic seizure or, preferably, its onset in advance of any clinical symptoms, or even just the increased likelihood that a seizure may occur. Responsive electrical stimulation treatment is applied elsewhere in the patient""s brain.
The application of stimulation signals remote from the epileptogenic region has several advantages. First, it is believed that such therapy will tend to avoid contributing to hypersynchronous activity in the epileptogenic region. Second, detection can be carried out at (or near) the same time stimulation is being performed, as it is less likely that the detection subsystems of the implantable neurostimulator will be affected by artifacts, specifically the stimulation signals transmitted through the brain tissue. Moreover, the ability to detect the effects of electrical stimulation on remote tissue in the patient""s brain may contribute to advantages in detecting, identifying and treating seizures and other neurological events with greater precision and reliability, and with longer advance notice.